One of the most common chronic liver disorders, affecting mainly people in Western countries, is nonalcoholic fatty liver disease (NAFLD). Unfortunately, its pathophysiological mechanism is not fully understood, and no dedicated treatment is available. Simple steatosis can lead to nonalcoholic steatohepatitis and even to fibrosis, cancer, and cirrhosis of the liver. NAFLD very often occurs in parallel with type 2 diabetes mellitus and in obese people. Furthermore, it is much more likely to develop in patients with metabolic syndrome (MS), whose criteria include abdominal obesity, elevated blood triacylglycerol level, reduced high-density lipoprotein cholesterol level, increased blood pressure, and high fasting glucose. An important phenomenon in MS is also insulin resistance (IR), which is very common in NAFLD. Liver IR and NAFLD development are linked through an interaction between the accumulation of free fatty acids, hepatic inflammation, and increased oxidative stress. The liver is particularly exposed to elevated levels of reactive oxygen species due to a large number of mitochondria in hepatocytes. In these organelles, the main DNA repair pathway is base excision repair (BER). The present article will illustrate how impairment of BER may be related to the development of NAFLD.
Background: Silibinin (SB), the main component of silymarin (SM) is a natural substance obtained from the seeds of the milk thistle. SM contains up 70% of SB as two isoforms: A and B. It has antioxidant and anti-inflammatory effect on hepatocytes, and is known to inhibit cell proliferation, induce apoptosis and curb angiogenesis. SB has demonstrated activity against many cancers, such as skin, liver, lung, bladder and breast carcinomas. Results: This review presents current knowledge of the use of SM in breast cancer, this being one of the most common types of cancer in women. It describes selected molecular mechanisms of the action of SM; for example, although SB influences both estrogen receptors (ER), α and β, it has opposite effects on the two. Its action on ERα influences the PI3K/AKT/mTOR and RAS/ERK signaling pathways, while by up-regulating ERβ, it increases the numbers of apoptotic cells. In addition, ERα is involved in SB-induced autophagy, while ERβ is not. Interestingly, SB also inhibits metastasis by suppressing TGF-β2 expression, thus suppressing epithelial to mesenchymal transition (EMT). It also influences migration and invasive potential via the Jak2/STAT3 pathway. Conclusion: SB may be a promising enhancement of BC treatment: when combined with chemotherapeutic drugs such as carboplatin, cisplatin and doxorubicin, the combination exerts a synergistic effect against cancer cells. This may be of value when treating aggressive types of mammary carcinoma.
The incidence of nonalcoholic fatty liver disease (NAFLD) is growing worldwide. Epidemiological data suggest a strong relationship between NAFLD and T2DM. This is associated with common risk factors and pathogenesis, where obesity, insulin resistance and dyslipidemia play pivotal roles. Expanding knowledge on the coexistence of NAFLD and T2DM could not only protect against liver damage and glucotoxicity, but may also theoretically prevent the subsequent occurrence of other diseases, such as cancer and cardiovascular disorders, as well as influence morbidity and mortality rates. In everyday clinical practice, underestimation of this problem is still observed. NAFLD is not looked for in T2DM patients; on the contrary, diagnosis for glucose metabolism disturbances is usually not performed in patients with NAFLD. However, simple and cost-effective methods of detection of fatty liver in T2DM patients are still needed, especially in outpatient settings. The treatment of NAFLD, especially where it coexists with T2DM, consists mainly of lifestyle modification. It is also suggested that some drugs, including hypoglycemic agents, may be used to treat NAFLD. Therefore, the aim of this review is to detail current knowledge of NAFLD and T2DM comorbidity, its prevalence, common pathogenesis, diagnostic procedures, complications and treatment, with special attention to outpatient clinics.
Non-alcoholic fatty liver disease (NAFLD) is a serious health problem due to its high incidence and consequences. In view of the existing controversies, new therapeutic options for NAFLD are still being sought. Therefore, the aim of our review was to evaluate the recently published studies on the treatment of NAFLD patients. We searched for articles in the PubMed database using appropriate terms, including “non-alcoholic fatty liver disease”, “nonalcoholic fatty liver disease”, “NAFLD”, “diet”, “treatment”, “physical activity”, “supplementation”, “surgery”, “overture” and “guidelines”. One hundred forty-eight randomized clinical trials published from January 2020 to November 2022 were used for the final analysis. The results show significant benefits of NAFLD therapy associated with the use of not only the Mediterranean but also other types of diet (including low-calorie ketogenic, high-protein, anti-inflammatory and whole-grain diets), as well as enrichment with selected food products or supplements. Significant benefits in this group of patients are also associated with moderate aerobic physical training. The available therapeutic options indicate, above all, the usefulness of drugs related to weight reduction, as well as the reduction in insulin resistance or lipids level and drugs with anti-inflammatory or antioxidant properties. The usefulness of therapy with dulaglutide and the combination of tofogliflozin with pioglitazone should be emphasized. Based on the results of the latest research, the authors of this article suggest a revision of the therapeutic recommendations for NAFLD patients.
Over the past two decades, extensive research has been done to elucidate the molecular etiology and pathophysiology of neuropsychiatric disorders. In majority of them, including Alzheimer’s disease (AD), Parkinson’s disease (PD), amyotrophic lateral sclerosis (ALS), bipolar disorder (BD), schizophrenia and major depressive disorder, increased oxidative and nitrosative stress was found. This stress is known to induce oxidative damage to biomolecules, including DNA. Accordingly, increased mitochondrial and nuclear DNA, as well as RNA damage, were observed in patients suffering from these diseases. However, recent findings indicate that the patients are characterised by impaired DNA repair pathways, which may suggest that these DNA lesions could be also a result of their insufficient repair. In the current systematic, critical review, we aim to sum up, using available literature, the knowledge about the involvement of nuclear and mitochondrial DNA damage and repair, as well as about damage to RNA in pathoetiology of neuropsychiatric disorders, i.e., AD, PD, ALS, BD, schizophrenia and major depressive disorder, as well as the usefulness of the discussed factors as being diagnostic markers and targets for new therapies. Moreover, we also underline the new directions to which future studies should head to elucidate these phenomena.
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